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Articles in PresS, published online ahead of print July 11, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00099.2002
Submitted on February 6, 2002
Accepted on July 3, 2002
1 Physiology, Northeastern Ohio Universities College of Medicine, Rootstown, OH, USA
2 Veterinary Physiology & Pharmacology, Texas A&M University, College Station, TX, USA
* To whom correspondence should be addressed. E-mail: jstallone{at}cvm.tamu.edu.
In rat thoracic aorta, contractile responses to vasopressin (VP) are three- to four-fold higher in females (F) than in males (M), and inhibition of cyclooxygenase attenuates these responses in F but not in M. Therefore, the effects of constrictor prostanoid (CP)pathway inhibitors on vascular reactivity to VP and phenylephrine (PE) were examined in thoracic aortae of M, F, and ovariectomized (OvX)-F rats. Contractile responses of endothelium-intact aortic rings from age-matched (13-18 wks) M, F, and OvX-F Sprague-Dawley rats were studied using standard isometric preparations. Cumulative concentration-responses were obtained to VP (10-11-10-6 M) or PE (10-11-10-5 M), either alone (control, Cont) or with various CP pathway inhibitors. Maximal contractile response of Cont aortae to VP was markedly higher in F (3,885 ± 332 mg/mg ring wt.) than in M (810 ± 148 mg). Indomethacin (Indo, 10 µM) attenuated maximal contractile response to VP in F (3,043 ± 277 mg) but not in M (886 ± 163 mg). SQ 29,548 (SQ, 1 mM) attenuated maximal response to VP in F (3,042 ± 290 mg) to a similar extent as Indo. Dazoxiben (Daz, 10 µM) alone had no effect, but Daz + SQ attenuated maximal contractile response to VP to a similar extent as SQ alone (2,536 ± 161 mg). Removal of the endothelium in F aortae attenuated contractile responses to VP in Cont aortae (3,469 ± 318 mg) and elimi- nated the attenuating effects of Indo (3,582 ± 198 mg), compared to endothelium-intact aortae (4,505 ± 209 mg). OvX attenuated maximal contractile response to VP in Cont aortae (2,093 ± 329 mg) and abolished the attenuating effects of Indo (1,511 ± 152 mg) or SQ (1,721 ± 72 mg). Indo, SQ, and Daz exerted identical effects on contractile responses of M, F, and OvX F aortae to PE. These findings establish that in the rat aorta: 1) CP, probably thromboxane (TXA2) and/or endoperoxide (PGH2), are responsible for ca. 25-30% of the contractile responses of F, but not M, to VP and PE; and 2) CP production by the F aorta is primarily endothelial in origin; and 3) Ovarian steroids modulate the production and/or actions of CP in the F aorta.
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